State-of-the-art technology in genomic sequencing has dramatically accelerated biomedical research to a point where tailored genomic approaches will soon be readily accessible to patients. Cancer treatment has already begun to incorporate sequence results into clinical decision-making; here, subsets of cancer are defined by individual genetic characteristics that inform treatment choices. Since common cancer subtypes have been the topic of large-scale genome projects, patients who have rare, poorly characterized cancers without standard therapies have much to gain through clinical tumor sequencing in Projects i and 2. However, if the clinical promise of such personalized medicine is to be realized, the psychosocial implications of genome sequence results must be better understood, effective health communication techniques developed, and ethical dilemmas addressed. For example, how will we decide when sequence results are ready for prime time (i.e., suitable for use and disclosure in a clinical setting)? Consensus policies that are based on ethical principles and incorporate patient viewpoints will need to be developed for genomic applications in clinical medicine. Also required will be an evidence-based plan for managing incidental findings and optimally presenting clinical or personally meaningful results. We know for example, that genetic education and counseling approaches that fail to incorporate best practices in health and risk communication can overwhelm patients' information-processing capacities. In addition, patient preferences for information may require physicians to consider not only the clinical utility of testing, but also how to address patients' personal utility values. This recognition will be especially important as sequencing inevitably generates findings (e.g., germline mutations) that are unrelated to the presenting cancer but nonetheless of interest to patients and/or their biological relatives. Furthermore, we need data on how patients actually respond to sequence results in order to understand how this novel information affects the likelihood and extent of potential psychosocial benefits (e.g., positive behavior changes) and harms (e.g., misunderstanding, distress). By addressing the aforementioned needs, our project will bring much-desired evidence to the vigorous debate about the appropriate use of genomic sequence information in medicine.